Status epilepticus (SE) is a major medical emergency, causing more than 35,000 deaths each year in the United States. The four research projects of this Epilepsy Research Center (ERC) at the Medical College of Virginia of Virginia Commonwealth University are focused on the CENTRAL THEME of studying SE. These projects compliment each other and the interaction of multi-disciplined investigators around a common theme greatly enhances the development of new insights and research productivity. The four projects will test specific hypotheses developed to investigate clinical aspects and basic mechanisms of SE are: SE: A Clinical and Epidemiological Study; Pathophysiology and Mortality of SE; Genetic Preponderance of SE in Twin Kindreds; and SE Duration- Dependent Modulation of GABAA Receptor Function. The clinical projects will offer important new insights into the epidemiology of SE in the elderly, the neonatal period, the young child, and different ethnic groups. This research will also produce a SE Outcome Scale for identifying high risk patients that can be used for clinical assessment and future therapeutic interventions. The intensive cardiac and central nervous system (CNS) physiological monitoring will test preliminary evidence that persistent CNS excitability predicts HIGH RISK patients for cardiac abnormalities that may ultimately lead to death in SE. In addition, this research effort has identified non-convulsive SE as a major cause of morbidity and mortality and has developed a prospective data base to evaluate this under recognized form of SE in the comatose patient. Utilizing one of the largest twin registries in the world, studies are proposed that provide the first direct evidence that the development of SE in man is controlled in part by a genetic predisposition. Animal models of SE demonstrate that there is a modulation of the GABAA receptor function that underlies the development of SE intractability and resistance to treatment. Studies indicate that alterations in the gamma amino butyric acid (GABA) receptor function play a major role in the pathogenesis of SE. The accomplishments of this research program are enhanced by the collaboration between committed investigators and research projects. The results from this study will ultimately develop new strategies to offer insights into the pathophysiology of SE and improve the diagnosis and treatment of this severe neurological condition.